Central nervous system (CNS)Abbreviations: CNS=central nervous system; PNS=peripheral nervous system; MS=multiple sclerosis; MBP=myelin basic protein; MHC=major histocompatibility complex; EAE=experimental allergic encephalomyelitis; O‐2A=oligodendrocyte‐type 2 astrocyte; GC=galactocerebroside; GFAP=glial fibrillary acidic protein; FGF=fibroblast growth factor; IGF1=insulin‐like growth factor. regeneration is a subject of great interest, particularly in diseases causing a dramatic loss of neurons. However, some CNS diseases do not affect neurons but damage other cells, such as the myelin‐forming cells — called oligodendrocytes — which (...) are also crucial to the harmonious function of the nervous system. Diseases in which oligodendrocytes and myelin are attacked can cause devastating neurological dysfunction which is sometimes followed by recovery and myelin repair or remyelination. The question of the regeneration potential of oligodendrocytes in experimental and human demyelinating diseases such as multiple sclerosis has been debated for a long time. Present evidence suggests that oligodendrocyte precursor cells persist in the adult CNS and that oligodendrocyte regeneration can occur but may be limited by ongoing disease processes. Here we will briefly review recent advances which have broadened our understanding of the cellular and molecular events of CNS remyelination. (shrink)

The sophisticated function of the central nervous system (CNS) is largely supported by proper interactions between neural cells and blood vessels. Accumulating evidence has demonstrated that neurons and glial cells support the formation of blood vessels, which in turn, act as migratory scaffolds for these cell types. Neural progenitors are also involved in the regulation of blood vessel formation. This mutual interaction between neural cells and blood vessels is elegantly controlled by several chemokines, growth factors, extracellular matrix, (...) and adhesion molecules such as integrins. Recent research has revealed that newly migrating cell types along blood vessels repel other preexisting migrating cell types, causing them to detach from the blood vessels. In this review, we discuss vascular formation and cell migration, particularly during development. Moreover, we discuss how the crosstalk between blood vessels and neurons and glial cells could be related to neurodevelopmental disorders. (shrink)

We consider the evidence that RA†, the vitamin A metabolite, is involved in three fundamental aspects of the development of the CNS: (1) the stimulation of axon outgrowth in particular neuronal sub‐types; (2) the migration of the neural crest; and (3) the specification of rostrocaudal position in the developing CNS (forebrain, midbrain, hindbrain, spinal cord). The evidence we discuss involves RA‐induction of neurites in cell cultures and explants of neural tissue; the teratological effects of RA on the embryo's nervous (...) system; the observation that RA can be detected endogenously in the spinal cord; and the fact that the receptors and binding proteins for RA are expressed in precise domains and neuronal cell types within the nervous system. (shrink)

Recent studies have found abnormal levels of brain-derived neurotrophic factor in a variety of central nervous system diseases. This suggests that BDNF may be involved in the pathogenesis of these diseases. Moreover, regulating BDNF signaling may represent a potential treatment for such diseases. With reference to recent research papers in related fields, this article reviews the production and regulation of BDNF in CNS and the role of BDNF signaling disorders in these diseases. A brief introduction of the (...) clinical application status of BDNF is also provided. (shrink)

The first paper in this pair (Bickhard in Axiomathes, 2015) developed a model of the nature of representation and cognition, and argued for a model of the micro-functioning of the brain on the basis of that model. In this sequel paper, starting with part III, this model is extended to address macro-functioning in the CNS. In part IV, I offer a discussion of an approach to brain functioning that has some similarities with, as well as differences from, the model presented (...) here: sometimes called the Predictive Brain approach. (shrink)

Standard semantic information processing models—information in; information processed; information out —lend themselves to standard models of the functioning of the brain in terms, e.g., of threshold-switch neurons connected via classical synapses. That is, in terms of sophisticated descendants of McCulloch and Pitts models. I argue that both the cognition and the brain sides of this framework are incorrect: cognition and thought are not constituted as forms of semantic information processing, and the brain does not function in terms of passive input (...) processing units organized as neural nets. An alternative framework is developed that models cognition and thought not in terms of semantic information processing, and, correspondingly, models brain functional processes also not in terms of semantic information processing. As alternative to such models: I outline a pragmatist oriented, interaction based, model of representation; derive from this model a fundamental framework of constraints on how the brain must function; show that such a framework is in fact found in the brain, and develop the outlines of a broader model of how mental processes can be realized within this alternative framework. Part I of this discussion focuses on some criticisms of standard modeling frameworks for representation and cognition, and outlines an alternative interactivist, pragmatist oriented, model. In part II, the focus is on the fact that the brain does not, in fact, function in accordance with standard passive input processing models—e.g., information processing models. Instead, there are multiple endogenously active processes at multiple spatial and temporal scales across multiple kinds of cells. A micro-functional model that accounts for, and even predicts, these multi-scale phenomena in generating emergent representation and cognition is outlined. That is, I argue that the interactivist model of representation outlined offers constraints on how the brain should function that are in fact empirically found, and, in reverse, that the multifarious details of brain functioning entail the pragmatist representational model—a very strong interrelationship. In the sequel paper, starting with part III, this model is extended to address macro-functioning in the CNS. In part IV, I offer a discussion of an approach to brain functioning that has some similarities with, as well as differences from, the model presented here: sometimes called the predictive brain approach. (shrink)

Philosophers of mind, both in the conceptual analysis tradition and in the empirical informed school, have been implicitly neglecting the potential conceptual role of the Peripheral Nervous System (PNS) in understanding sensory and perceptual states. Instead, the philosophical as well as the neuroscientific literature has been assuming that it is the Central Nervous System (CNS) alone, and more exactly the brain, that should prima facie be taken as conceptually and empirically crucial for a philosophical analysis (...) of such states This is the first monograph that focuses on the PNS and its constitutive role in sensory states, including pain, mechanoception, proprioception, tactile perception, and so forth. -/- The author argues that the brain-centeredness of current philosophy of mind is a prejudice, and proposes a series of original ways in which classic puzzles in the philosophy of mind can be solved once the hypothesis that PNS is a constitutive element of mental states is taken seriously. The author calls this “the Peripheral Mind Hypothesis”, and employs it in a vast range of issues, such as functionalism, physicalism, mental content, embodiment, as well as some issues in neuroethics. -/- Making equal use of conceptual analysis, empirical data from neuroscience, first-person phenomenological data, and philosophical speculation, this work offers a fresh look at, and novel solutions to many philosophical problems. (shrink)

New possibilities to modify function and direct repair in the central nervous system (CNS) have been established by the merger of gene transfer technology with neural transplantation. Rapid advances in viral‐mediated DNA‐delivery procedures permit the study of novel gene expression in neurons and glial cells. Foreign genes, transferred by a virus vector, can be used to generate new cell lines, identify transplanted cells, and express growth factors or enzymes for neurotransmitter synthesis. In addition to CNS cell types, (...) non‐neural cells are also being studied with transgene technology in the nervous system. Functional effects have been obtained with grafts of genetically modified cells in animal models of several nervous system disorders, and the recent results set the stage for potential application of these techniques to human CNS gene therapy. (shrink)

Researchers are enthusiastically concerned about neural stem cell (NSC) therapy in a wide array of diseases, including stroke, neurodegenerative disease, spinal cord injury (SCI) and depression. Although enormous evidences have demonstrated that neurobehavioral improvement may benefit from NSC-supporting regeneration in animal models, approaches to endogenous and transplanted NSCs are blocked by hurdles of migration, proliferation, maturation and integration of NSCs. Electrical stimulation (ES) may be a selective nondrug approach for mobilizing NSCs in the central nervous system (CNS). (...) This technique is suitable for clinic application, because it is well established and its potential complications are manageable. Here, we provide a comprehensive review of the emerging positive role of different electrical cues in regulating NSC biology in vitro and in vivo, as well as biomaterial-based and chemical stimulation of NSCs. In the future, ES combined with stem cell therapy or other cues probably becomes an approach for promoting brain repair. (shrink)

Complementation and correction of a genetic defect with CNS manifestations lags behind gene therapy for inherited disorders affecting other organ systems because of shortcomings in delivery vehicles and access to the CNS. The effects of improvements in viral and nonviral vectors, coupled with the development of delivery strategies designed to transfer genetic material thoughout the CNS are being investigated by a number of laboratories in efforts to overcome these problems.

This target article draws together two groups of experimental studies on the control of human movement through peripheral feedback and centrally generated signals of motor commands. First, during natural movement, feedback from muscle, joint, and cutaneous afferents changes; in human subjects these changes have reflex and kinesthetic consequences. Recent psychophysical and microneurographic evidence suggests that joint and even cutaneous afferents may have a proprioceptive role. Second, the role of centrally generated motor commands in the control of normal movements and movements (...) following acute and chronic deafferentation is reviewed. There is increasing evidence that subjects can perceive their motor commands under various conditions, but that this is inadequate for normal movement; deficits in motor performance arise when the reliance on proprioceptive feedback is abolished either experimentally or because of pathology. During natural movement, the CNS appears to have access to functionally useful input from a range of peripheral receptors as well as from internally generated command signals. The unanswered questions that remain suggest a number of avenues for further research. (shrink)

Excessive alcohol use has adverse effects on the central nervous system (CNS) and can lead to alcohol use disorders (AUDs). Recent studies have suggested that myelin reductions may directly contribute to CNS dysfunctions associated with AUDs. Myelin consists of compact lipid membranes wrapped around axons to provide electrical insulation and trophic support. Regulation of myelin is considered as a new form of neural plasticity due to its profound impacts on the computation of neural networks. In this review, (...) the authors first discuss experimental evidence showing how alcohol exposure causes demyelination in different brain regions, often accompanied by deficits in cognition and emotion. Next, they discuss postulated molecular and cellular mechanisms underlying alcohol's impact on myelin. It is clear that more extensive investigations are needed in this important but underexplored research field in order to gain a better understanding of the myelin‐behavior relationship and to develop new treatment strategies for AUDs. (shrink)

Achieving regeneration of the central nervous system (CNS) is a major challenge for regenerative medicine. The inability of mammals to regrow a severed CNS contrasts with the amazing regenerative powers of their deuterostome kin, the echinoderms. Rapid CNS regeneration from a specialized autotomy plane in echinoderms presents a highly tractable and suitable non‐model system for regenerative biology and evolution. Starfish arm autotomy triggers mass cell migration and local proliferation, facilitating rapid CNS regeneration. Many regeneration events in (...) nature are preceded by autotomy and there are striking parallels between autotomy and regeneration in starfish and lizards. Comparison of these systems holds promise to provide insight into regeneration deficiency in higher vertebrates and to uncover evolutionarily conserved deuterostome‐chordate regenerative processes. This will help identify mechanisms that may be present but inactive in higher vertebrates to address the problem of their poor regenerative capacities and the challenge to achieve CNS repair and regrowth. (shrink)

Rapid changes of state in central nervous systems (CNS), as required following stimuli that must arouse the CNS from a quiescent state in order to activate a behavioral response, constitute a particularly appropriate application of non‐linear dynamics. Chaotic dynamics would provide tremendous amplification of neuronal activity needed for CNS arousal, sensitively dependent on the initial state of the CNS. This theoretical approach is attractive because it supposes dynamics that are deterministic and it links the elegant mathematics of chaos (...) to the conception of a fundamental property of the CNS. However, a living system must be able to exit from chaotic dynamics in order to avoid widely divergent, biologically impossible outcomes. We hypothesize that, analogous to phase transitions in a liquid crystal, CNS arousal systems, having ‘woken up the brain’ to activate behavior, go through a phase transition and emerge under the control of orderly movement control systems. BioEssays 29:803–810, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

The way the central nervous system (CNS) responds to diverse stimuli is contingent upon the specific brain state of the individual, including sleep and wakefulness. Despite the wealth of readout parameters and data delineating the brain states, the primary mechanisms are yet to be identified. Here we highlight the role of astrocytes, with a specific emphasis on chloride (Cl−) homeostasis as a modulator of brain states. Neuronal activity is regulated by the concentration of ions that determine excitability. (...) Astrocytes, as the CNS homeostatic cells, are recognised for their proficiency in maintaining dynamic homeostasis of ions, known as ionostasis. Nevertheless, the contribution of astrocyte‐driven ionostasis to the genesis of brain states or their response to sleep‐inducing pharmacological agents has been overlooked. Our objective is to underscore the significance of astrocytic Cl− homeostasis, elucidating how it may underlie the modulation of brain states. We endeavour to contribute to a comprehensive understanding of the interplay between astrocytes and brain states. (shrink)

A deficit in the number of organs available for transplantation persists even with an increase in donation rates. One possible choice of donor for organs that appears under-referred and/or unaccepted is patients with primary brain tumours. In spite of advances in the treatment of high-grade primary central nervous system (CNS) tumours, the prognosis remains dire. A working group on organs from donors with primary CNS tumours showed that the risk of transmission is small and outweighs the benefits (...) of waiting for a normal donor, in survival and organ life-years, with caveats. This paper explores the possibility that, if information on organ donation were made available to patients and their families with knowledge of their inevitable fate, perhaps some will choose to donate. It would be explained that to achieve this, elective ventilation would be performed in their final moments. This would obviate the consent question because of an advance statement. It is accepted that these are sensitive matters and there will be logistic issues. This will need discussion with the public and other professionals, but it could increase the number of donors and can be extrapolated to encompass other primary CNS tumours. (shrink)

In the mammalian central nervous system (CNS), each neuron receives signals from other neurons through numerous synapses located on its cell body and dendrites. Molecules involved in the postsynaptic signaling pathways need to be targeted to the appropriate subcellular domains at the right time during both synaptogenesis and the maintenance of synaptic functions. The presence of messenger RNAs (mRNAs) in dendrites offers a mechanism for synthesizing the appropriate molecules at the right place in response to local extracellular (...) stimuli. Several dendritic mRNAs have been identified, and the mechanisms controlling their localization are beginning to be understood. In many cell types, controls on mRNA stability play an important role in the regulation of gene expression, but it is unclear to what extent this type of control operates in dendrites. The regulation of protein synthesis and the control of mRNA stability in dendrites could have important implications for neuronal function. BioEssays 20:70–78, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

The brain ventricular system is a series of connected cavities, filled with cerebrospinal fluid (CSF), that forms within the vertebrate central nervous system (CNS). The hollow neural tube is a hallmark of the chordate CNS, and a closed neural tube is essential for normal development. Development and function of the ventricular system is examined, emphasizing three interdigitating components that form a functional system: ventricle walls, CSF fluid properties, and activity of CSF constituent factors. The (...) cellular lining of the ventricle both can produce and is responsive to CSF. Fluid properties and conserved CSF components contribute to normal CNS development. Anomalies of the CSF/ventricular system serve as diagnostics and may cause CNS disorders, further highlighting their importance. This review focuses on the evolution and development of the brain ventricular system, associated function, and connected pathologies. It is geared as an introduction for scholars with little background in the field. (shrink)

The relatively simple central nervous system (CNS) of the Drosophila embryo provides a useful model system for investigating the mechanisms that generate and pattern complex nervous systems. Central to the generation of different types of neurons by precursor neuroblasts is the initial specification of neuroblast identity and the Drosophila segment polarity genes, genes that specify regions within a segment or repeating unit of the Drosophila embryo, have emerged recently as significant players in this process. (...) During neurogenesis the segment polarity genes are expressed in the neuroectodermal cells from which neuroblasts delaminate and they continue to be expressed in neuroblasts and their progeny. Loss-of-function mutations in these genes lead to a failure in the formation of neuroblasts and/or specification of neuroblast identity. Results from several recent studies suggest that regulatory interactions between segment polarity genes during neurogenesis lead to an increase in the number of neuroblasts and specification of different identities to neuroblasts within a population of cells. BioEssays 21:472–485, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

Criminal offenders may be offered to participate in voluntary rehabilitation programs aiming at correcting undesirable behaviour, as a condition of early release. Behavioural treatment may include direct intervention into the central nervous system (CNS). This article discusses under which circumstances voluntary rehabilitation by CNS intervention is justified. It is argued that although the context of voluntary rehabilitation is a coercive circumstance, consent may still be effective, in the sense that it can meet formal criteria for informed consent. (...) Further, for a consent to be normatively valid (“take the wronging out of the act”) under a coercive circumstance, the subject to be treated must (1) have the sovereign authority to consent, and (2) the offer-giver must be in the right normative position to make the offer. While I argue that subjects do have the sovereign authority to consent to treatment, I also argue that inappropriate offers yield invalid consents. Considerations on inappropriate offers should therefore inform which kinds of CNS intervention-based rehabilitation schemes the state may propose as part of the criminal justice system. Yet as I conclude in this paper, while there are some intrinsic constraints on voluntary rehabilitation programs, the main constraints on voluntary rehabilitation are likely to be contingent overriders. However, CNS intervention is not ruled out as such in the context of voluntary rehabilitation. (shrink)

In the mammalian central nervous system (CNS), each neuron receives signals from other neurons through numerous synapses located on its cell body and dendrites. Molecules involved in the postsynaptic signaling pathways need to be targeted to the appropriate subcellular domains at the right time during both synaptogenesis and the maintenance of synaptic functions. The presence of messenger RNAs (mRNAs) in dendrites offers a mechanism for synthesizing the appropriate molecules at the right place in response to local extracellular (...) stimuli. Several dendritic mRNAs have been identified, and the mechanisms controlling their localization are beginning to be understood. In many cell types, controls on mRNA stability play an important role in the regulation of gene expression, but it is unclear to what extent this type of control operates in dendrites. The regulation of protein synthesis and the control of mRNA stability in dendrites could have important implications for neuronal function. BioEssays 20:70–78, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

The association between emotional expression and physiological emotional states is at best, modest. Using data from the autonomic nervous system (ANS), central nervous system (CNS), and hormonal systems there appears to be an association which accounts for approximately 10—20% of the variance between them. Excluding measurement error, it is proposed that the need for action and regulation accounts for the low levels of synchrony. Understanding system responses allows for the study of individual differences as (...) a way of understanding both emotional expressions and states. (shrink)

First isolated in the fly and now characterised in vertebrates, the Slit proteins have emerged as pivotal components controlling the guidance of axonal growth cones and the directional migration of neuronal precursors. As well as extensive expression during development of the central nervous system (CNS), the Slit proteins exhibit a striking array of expression sites in non-neuronal tissues, including the urogenital system, limb primordia and developing eye. Zebrafish Slit has been shown to mediate mesodermal migration during (...) gastrulation, while Drosophila slit guides the migration of mesodermal cells during myogenesis. This suggests that the actions of these secreted molecules are not simply confined to the sphere of CNS development, but rather act in a more general fashion during development and throughout the lifetime of an organism. This review focuses on the non-neuronal activities of Slit proteins, highlighting a common role for the Slit family in cellular migration. (shrink)

Recent advances in AI raise the possibility that AI systems will one day be able to do anything humans can do, only better. If artificial general intelligence (AGI) is achieved, AI systems may be able to understand, reason, problem solve, create, and evolve at a level and speed that humans will increasingly be unable to match, or even understand. These possibilities raise a natural question as to whether AI will eventually become superior to humans, a successor “digital species”, with a (...) rightful claim to assume leadership of the universe. However, a deeper consideration suggests the overlooked differentiator between human beings and AI is not the brain, but the central nervous system (CNS), providing us with an immersive integration with physical reality. It is our CNS that enables us to experience emotion including pain, joy, suffering, and love, and therefore to fully appreciate the consequences of our actions on the world around us. And that emotional understanding of the consequences of our actions is what is required to be able to develop sustainable ethical systems, and so be fully qualified to be the leaders of the universe. A CNS cannot be manufactured or simulated; it must be grown as a biological construct. And so, even the development of consciousness will not be sufficient to make AI systems superior to humans. AI systems may become more capable than humans on almost every measure and transform our society. However, the best foundation for leadership of our universe will always be DNA, not silicon. (shrink)

Nijhawan argues convincingly that predictive mechanisms are pervasive in the central nervous system (CNS). However, scientific understanding of visual prediction requires one to formulate empirically testable neurophysiological models. The author's suggestions in this direction are to be evaluated on the basis of more realistic experimental methodologies and more plausible assumptions on the hierarchical character of the human visual cortex.

The Drosophila embryo provides a useful model system to study the mechanisms that lead to pattern and cell diversity in the central nervous system (CNS). The Drosophila CNS, which encompasses the brain and the ventral nerve cord, develops from a bilaterally symmetrical neuroectoderm, which gives rise to neural stem cells, called neuroblasts. The structure of the embryonic ventral nerve cord is relatively simple, consisting of a sequence of repeated segmental units (neuromeres), and the mechanisms controlling the (...) formation and specification of the neuroblasts that form these neuromeres are quite well understood. Owing to the much higher complexity and hidden segmental organization of the brain, our understanding of its development is still rudimentary. Recent investigations on the expression and function of proneural genes, segmentation genes, dorsoventral‐patterning genes and a number of other genes have provided new insight into the principles of neuroblast formation and patterning during embryonic development of the fly brain. Comparisons with the same processes in the trunk help us to understand what makes the brain different from the ventral nerve cord. Several parallels in early brain patterning between the fly and the vertebrate systems have become evident. BioEssays 26:739–751, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

I examine critically the application of information‐theoretic ideas to biological communication during embryonic development and in the functioning central nervous system (CNS). I show that intercellular communication relies mostly on simple signals whose role is to effect a selection among predetermined cellular states. Hence, a crucial role is played by cellular memory, which stabilizes such states. Memory in cells is partly located in the nuclear DNA; no less important however is (phenotypic) memory lying in the cell's organelles (...) and compartments. Because of combinatorial effects in gene expression patterns, cell memory is an enormously powerful mechanism, which also underlies plasticity, and thus constitutes the factor unifying genetic determination, plasticity and learning. Communication in the CNS is analyzed in some detail: here, cellular memory is embodied in anatomy (i.e., cell shape) and neurochemistry. These are the major, relatively “static” factors affecting the routing of neural impulses in the adult CNS. In addition, however, faster channeling is also required: action potentials must be directed to their targets along a few of exponentially many paths, and this dynamic routing is crucial for proper operation. I suggest that collective oscillatory modes may play a role in solving this addressing problem, in the same way that the clock signal gates the operation of man‐made computers. BioEssays 25:699–708, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Autism has been defined as a disorder of social cognition, interaction and communication where ritualistic, repetitive behaviors are commonly observed. But how should we understand the behavioral and cognitive differences that have been the main focus of so much autism research? Can high-level cognitive processes and behaviors be identified as the core issues people with autism face, or do these characteristics perhaps often rather reflect individual attempts to cope with underlying physiological issues? Much research presented in this volume will point (...) to the latter possibility, i.e. that people on the autism spectrum cope with issues at much lower physiological levels pertaining not only to Central Nervous Systems (CNS) function, but also to peripheral and autonomic systems (PNS, ANS) (Torres, Brincker, et al. 2013). The question that we pursue in this chapter is what might be fruitful ways of gaining objective measures of the large-scale systemic and heterogeneous effects of early atypical neurodevelopment; how to track their evolution over time and how to identify critical changes along the continuum of human development and aging. We suggest that the study of movement variability—very broadly conceived as including all minute fluctuations in bodily rhythms and their rates of change over time (coined micro-movements (Figure 1A-B) (Torres, Brincker, et al. 2013))—offers a uniquely valuable and entirely objectively quantifiable lens to better assess, understand and track not only autism but cognitive development and degeneration in general. This chapter presents the rationale firstly behind this focus on micro-movements and secondly behind the choice of specific kinds of data collection and statistical metrics as tools of analysis (Figure 1C). In brief the proposal is that the micro-movements (defined in Part I – Chapter 1), obtained using various time scales applied to different physiological data-types (Figure 1), contain information about layered influences and temporal adaptations, transformations and integrations across anatomically semi-independent subsystems that crosstalk and interact. Further, the notion of sensorimotor re-afference is used to highlight the fact that these layered micro-motions are sensed and that this sensory feedback plays a crucial role in the generation and control of movements in the first place. In other words, the measurements of various motoric and rhythmic variations provide an access point not only to the “motor systems”, but also access to much broader central and peripheral sensorimotor and regulatory systems. Lastly, we posit that this new lens can also be used to capture influences from systems of multiple entry points or collaborative control and regulation, such as those that emerge during dyadic social interactions. (shrink)

A comprehensive understanding of the cerebrospinal fluid system is essential for our understanding of health and disease within the central nervous system. The system of CSF refers to all components involved in CSF production, movement, and absorption. In recent years, extensive research has resulted in vastly improved understanding of the CSF system in health and disease. Yet, several aspects remain to be fully clarified, notably along the spinal cord as the preponderance of research has (...) focused on the brain. This review briefly summarizes the CSF system and its implications for CNS diseases and highlights the knowledge gaps that require further research. (shrink)

The mature cerebral cortex contains a staggering variety of projection neuron subtypes, and a number of complementary studies have recently begun to define their identity and embryonic origin. Among the different types of cortical projection neurons, subcerebral projection neurons, including corticospinal motor neurons (CSMN), have been extensively studied and some of the molecular controls over their differentiation have been elucidated. Here, we first provide an overview of the approaches used to purify and molecularly profile neuronal populations of the neocortex and, (...) more broadly, of the central nervous system (CNS). Next, we specifically review recent progress in understanding the genes that define and control development of the CSMN population. Finally, we briefly discuss the relevance of this work to current questions regarding the mechanisms of the establishment of projection neuron subtype identity in the neocortex and its implications to direct the differentiation of CSMN for therapeutic benefit. (shrink)

ObjectiveTo elucidate the clinical, radiologic characteristics of Leber’s hereditary optic neuropathy (LHON) associated with the other diseases.Materials and methodsClinical data were retrospectively collected from hospitalized patients with LHON associated with the other diseases at the Neuro-Ophthalmology Department at the Chinese People’s Liberation Army General Hospital (PLAGH) from December 2014 to October 2018.ResultsA total of 13 patients, 24 eyes (10 men and 3 women; mean age, 30.69 ± 12.76 years) with LHON mitochondrial DNA (mtDNA) mutations, were included in the cohort. 14502(5)11778(4)11778 (...) &11696(1)12811(1)11696(1)3460(1). One patient was positive for aquaporin-4 antibody (AQP4-Ab), and two were positive for myelin oligodendrocyte glycoprotein antibody (MOG-Ab). Three patients were associated with idiopathic optic neuritis (ON). Two patients were with compression optic neuropathy. Three patients were with the central nervous system (CNS) diseases. One patient was with proliferative diabetic retinopathy (PDR) and one with idiopathic orbital inflammatory syndrome (IOIS). At the onset, visual acuity (VA) in eighteen eyes was below 0.1, one eye was 0.5, five eyes were above 0.5, while VA in sixteen eyes was below a 0.1 outcome, three eyes experienced moderate vision loss. MRI images showed T2 lesions and enhancement in nine patients who received corticosteroids treatment; additional immune modulators treatment was performed on two patients. None of the patients had relapse during the follow-up time.ConclusionLeber’s hereditary optic neuropathy can be accompanied with multiple-related diseases, especially different subtypes of ON, which were also exhibited with IOIS and compression optic neuropathy for the first time in this cohort. This condition may be a distinct entity with an unusual clinical and therapeutic profile. (shrink)

We present evidence disputing the hypothesis that memories are processed or consolidated in REM sleep. A review of REM deprivation (REMD) studies in animals shows these reports to be about equally divided in showing that REMD does, or does not, disrupt learning/memory. The studies supporting a relationship between REM sleep and memory have been strongly criticized for the confounding effects of very stressful REM deprivation techniques. The three major classes of antidepressant drugs, monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), and (...) selective serotonin reuptake inhibitors (SSRIs), profoundly suppress REM sleep. The MAOIs virtually abolish REM sleep, and the TCAs and SSRIs have been shown to produce immediate (40–85%) and sustained (30–50%) reductions in REM sleep. Despite marked suppression of REM sleep, these classes of antidepressants on the whole do not disrupt learning/memory. There have been a few reports of patients who have survived bilateral lesions of the pons with few lingering complications. Although these lesions essentially abolished REM sleep, the patients reportedly led normal lives. Recent functional imaging studies in humans have revealed patterns of brain activity in REM sleep that are consistent with dream processes but not with memory consolidation. We propose that the primary function of REM sleep is to provide periodic endogenous stimulation to the brain which serves to maintain requisite levels of central nervous system (CNS) activity throughout sleep. REM is the mechanism used by the brain to promote recovery from sleep. We believe that the cumulative evidence indicates that REM sleep serves no role in the processing or consolidation of memory. Key Words: antidepressant drugs; brain stem lesions; dreams; functional imaging; memory consolidation; REM deprivation; REM sleep; theta rhythm. (shrink)

Injury to the central or peripheral nervous system is often associated with persistent pain. After ischemic injury to the spinal cord, rats develop severe mechanical allodynia-like symptoms, expressed as a pain-like response to innocuous stimuli. In its short-lasting phase the allodynia can be relieved with the [gamma]-aminobutyric acid (GABA)-B receptor agonist baclofen, which also reverses the hyperexcitability of dorsal horn interneurons to mechanical stimuli. Furthermore, there is a reduction in GABA immunoreactivity in the dorsal horn of allodynic (...) rats. Clinical neuropathic pain of peripheral and central origin often cannot be relieved by opiates at doses that do not cause side effects. The loss of sensitivity to opiates may be associated with the up-regulation of endogenous antiopioid substances, such as the neuropeptide cholecystokinin (CCK). CCK and its receptor (CCK-R) protein is normally not detectable in rat dorsal root ganglion cells. After peripheral nerve section, both CCK and CCK-R are up-regulated in the dorsal root ganglia. Furthermore, CI 988, an antagonist of the CCK-B receptor, chronically coadministered with morphine, reduces autotomy, a behavior that may be a sign of neuropathic pain following peripheral nerve section. Thus, opiate insensitivity may be due to the release of CCK from injured primary afferents. Similarly, in the chronic phase of the spinal ischemic model of central pain, the allodynia-like symptom is not relieved by systemic morphine, but is significantly reversed by the CCK-B antagonist. Consequently, up-regulation of CCK and CCK-R in the CNS may also underlie opiate drug insensitivity following CNS injury. Thus, dysfunction of central inhibition involving GABA and endogenous opioids may be a factor underlying the development of sensory abnormalities and/or pain following injury to neural tissue. (shrink)

Two aspects of the target article, (1) the extension of the equilibrium point theory to multi-joint movements, and (2) the consequence that the EMG pattern is not directly controlled by the central nervous system (CNS), are discussed in light of the experiments on upper trunk bending in humans. The principle component kinematic analysis and the analysis of the EMG data, obtained under microgravity and additional loading conditions, support the application of Feldman and Levin's for multi-joint pointing movement (...) to equilibrium control during upper trunk movement. (shrink)

Brain function depends on the cooperation between highly specialized cells. Neurons generate electrical signals and glial cells provide structural and metabolic support. Here, I propose a new kind of job‐sharing between neurons and astrocytes. Recent studies on primary cultures of highly purified neurons from the rodent central nervous system (CNS) suggest that, during development, neurons reduce or even abandon cholesterol synthesis to save energy and import cholesterol from astrocytes via lipoproteins. The cholesterol shuttle may be restricted to (...) compartments distant from the soma including synapses and may be regulated by electrical activity. Testing these hypotheses will help to improve our still insufficient understanding of brain cholesterol metabolism and its role in neurodegeneration. BioEssays 25:72–78, 2003. © 2002 Wiley Periodicals, Inc. (shrink)

In order to achieve flexible and smooth walking, we must accomplish subtasks (e.g., loading response, forward propulsion or swing initiation) within a gait cycle. To evaluate subtasks within a gait cycle, the analysis of muscle synergies may be effective. In the case of walking, extracted sets of muscle synergies characterize muscle patterns that relate to the subtasks within a gait cycle. Although previous studies have reported that the muscle synergies of individuals with disorders reflect impairments, a way to investigate the (...) instability in the activations of muscle synergies themselves has not been proposed. Thus, we investigated the local dynamic stability and orbital stability of activations of muscle synergies across various walking speeds using maximum Lyapunov exponents and maximum Floquet multipliers. We revealed that the local dynamic stability in the activations decreased with accelerated walking speeds. Contrary to the local dynamic stability, the orbital stability of the activations was almost constant across walking speeds. In addition, the increasing rates of maximum Lyapunov exponents were different among the muscle synergies. Therefore, the local dynamic stability in the activations might depend on the requirement of motor output related to the subtasks within a gait cycle. We concluded that the local dynamic stability in the activation of muscle synergies decrease as walking speed accelerates. On the other hand, the orbital stability is sustained across broad walking speeds. (shrink)

Humans routinely modify their walking speed to adapt to functional goals and physical demands. However, damage to the central nervous system often results in abnormal modulation of walking speed and increased risk of falls. There is considerable interest in treatment modalities that can provide safe and salient training opportunities, feedback about walking performance, and that may augment less reliable sensory feedback within the CNS after injury or disease. Fully immersive virtual reality technologies show benefits in boosting training-related (...) gains in walking performance; however, they lack views of the real world that may limit functional carryover. Augmented reality and mixed reality head-mount displays provide partially immersive environments to extend the virtual reality benefits of interacting with virtual objects but within an unobstructed view of the real world. Despite this potential advantage, the feasibility of using MR-HMD visual feedback to promote goal-directed changes in overground walking speed remains unclear. Thus, we developed and evaluated a novel mixed reality application using the Microsoft HoloLens MR-HMD that provided real-time walking speed targets and augmented visual feedback during overground walking. We tested the application in a group of adults not living with disability and examined if they could use the targets and visual feedback to walk at 85%, 100%, and 115% of each individual’s self-selected speed. We examined whether individuals were able to meet each target gait speed and explored differences in accuracy across repeated trials and at the different speeds. Additionally, given the importance of task-specificity to therapeutic interventions, we examined if walking speed adjustment strategies were consistent with those observed during usual overground walking, and if walking with the MR-HMD resulted in increased variability in gait parameters. Overall, participants matched their overground walking speed to the target speed of the MR-HMD visual feedback conditions. The percent inaccuracy was approximately 5% across all speed matching conditions and remained consistent across walking trials after the first overall walking trial. Walking with the MR-HMD did not result in more variability in walking speed, however, we observed more variability in stride length and time when walking with feedback from the MR-HMD compared to walking without feedback. The findings offer support for mixed reality-based visual feedback as a method to provoke goal-specific changes in overground walking behavior. Further studies are necessary to determine the clinical safety and efficacy of this MR-HMD technology to provide extrinsic sensory feedback in combination with traditional treatments in rehabilitation. (shrink)

Common symptoms of multiple sclerosis (MS) include motor impairments of the lower extremities, particularly gait disturbances. Loss of balance and muscle weakness, representing some peripheral effects, have been shown to influence these symptoms, however, the individual role of cortical and subcortical structures in the central nervous system is still to be understood. Assessing [18F]fluorodeoxyglucose (FDG) uptake in the CNS can assess brain activity and is directly associated with regional neuronal activity. One potential modality to increase cortical excitability (...) and improve motor function in patients with MS (PwMS) is transcranial direct current stimulation (tDCS). However, tDCS group outcomes may not mirror individual subject responses, which impedes our knowledge of the pathophysiology and management of diseases like MS. Three PwMS randomly received both 3 mA tDCS and SHAM targeting the motor cortex (M1) that controls the more-affected leg for 20 min on separate days before walking on a treadmill. The radiotracer, FDG, was injected at minute two of the 20 min walk and the subjects underwent a Positron emission tomography (PET) scan immediately after the task. Differences in relative regional metabolism of areas under the tDCS anode and the basal ganglia were calculated and investigated. The results indicated diverse and individualized responses in regions under the anode and consistent increases in some basal ganglia areas (e.g., caudate nucleus). Thus, anodal tDCS targeting the M1 that controls the more-affected leg of PwMS might be capable of affecting remote subcortical regions and modulating the activity (motor, cognitive, and behavioral functions) of the circuitry connected to these regions. (shrink)

Many biologically active compounds including neurotransmitters, metabolic precursors, and certain drugs are accumulated intracellularly by transporters that are coupled to the transmembrane Na+ gradient. Amino acid neurotransmitter transporters play a key role in the regulation of extracellular amino acid concentrations and termination of neurotransmission in the CNSAbbreviations: CNS, central nervous system; GABA, γ‐aminobutyric acid; cDNA, complementary deoxyribonucleic acid; mRNA, messenger ribonucleic acid; NMDA, N‐methyl‐D‐aspartate; PKC, protein kinase C; PMA, phorbol 12‐myristate 13‐acetate; DAG, diacyl glycerol; R59022, DAG kinase (...) inhibitor; AA, arachidonic acid; ACHC, cis‐3‐aminocyclohexanecarboxylic acid; GAT‐A, ACHC‐sensitive GABA transporter; GAT‐B, β‐alanine‐sensitive GABA transporter; GLY‐1 and GLYT‐1, glycine transporters; PROT‐1, proline transporter; BGT‐1, betaine transporter.. Transporters for the major amino acid neurotransmitters glutamate, GABA, and glycine are found in both neurons and glial cells. Recent work has resulted in the identification of cDNAs encoding several amino acid neurotransmitter transport proteins, all of which belong to the Na+‐and Cl−‐dependent transporter gene family. The diversity of this family suggests a degree of transporter heterogeneity that is greater than that indicated by biochemical and pharmacological studies. (shrink)

Transient global amnesia is a benign memory disorder with etiologies that have been debated for a long time. The prevalence of stressful events before a TGA attack makes it hard to overlook these precipitating factors, given that stress has the potential to organically effect the brain. Cortical spreading depression was proposed as a possible cause decades ago. Being a regional phenomenon, CSD seems to affect every aspect of the micro-mechanism in maintaining the homeostasis of the central nervous (...) class='Hi'>system. Corresponding evidence regarding hemodynamic and morphological changes from TGA and CSD have been accumulated separately, but the resemblance between the two has not been systematically explored so far, which is surprising especially considering that CSD had been confirmed to cause secondary damage in the human brain. Thus, by deeply delving into the anatomic and electrophysiological properties of the CNS, the CSD-TGA model may render insights into the basic pathophysiology behind the façade of the enigmatic clinical presentation. (shrink)

Where does the cognitive system begin and end? Intracranialists maintain that the cognitive system is entirely identifiable with the biological central nervous system. Transcranialists, on the other hand, suggest that the cognitive system can extend beyond the biological CNS. In the second division of Supersizing the Mind, Clark defends the transcranial account against various objections. Of interest for this paper is Clark’s response to what he calls “asymmetry arguments.”Asymmetry arguments can be summarized as follows: (...) subtract the props and aids, and the organism may create replacements. But subtract the organism, and all cognitive activity ceases. Although I am sympathetic to Clark’s overall project, I find his response to the asymmetry arguments inadequate in light of his responses to other objections. For this reason, I maintain that Clark’s response requires revision. By adopting a process metaphysics and appealing to mereological dependencies, I believe that Clark can provide a substantive response to asymmetry arguments that is consistent with his overall theory. This paper unfolds as follows: after summarizing Clark’s response to the asymmetry objection in, I will argue that his response is unsuccessful in. My argument hinges on the claim that Clark does not take into account the full intent of Rupert’s asymmetry argument. In I modify Clark’s response by appealing to mereology and the asymmetrical dependencies found therein. I conclude in that this modification provides Clark with an adequate response to the asymmetry argument and is consistent with his overall transcranialist account. The further question of whether this account assists Clark in responding to other intracranialist objections is beyond the scope of this paper. (shrink)

The concept of “information” is virtually ubiquitous in contemporary cognitive science. It is claimed to be “processed” (in cognitivist theories of perception and comprehension), “stored” (in cognitivist theories of memory and recognition), and otherwise manipulated and transformed by the human central nervous system. Fred Dretske's extensive philosophical defense of a theory of informational content (“semantic” information) based upon the Shannon-Weaver formal theory of information is subjected to critical scrutiny. A major difficulty is identified in Dretske's equivocations in (...) the use of the concept of a “signal” bearing informational content. Gibson's alternative conception of information (construed as analog by Dretske), while avoiding many of the problems located in the conventional use of “signal”, raises different but equally serious questions. It is proposed that, taken literally, the human CNS does not extract or process information at all; rather, whatever “information” is construed as locatable in the CNS is information only for an observer-theorist and only for certain purposes. (shrink)

The Mechanics of the Mind, in the words of its author, "is an attempt to interpret the phenomenon of mind in terms of the physiological processes of the nervous system and to explore the philosophical implications of a realistically conceived theory." The first four chapters of the book is little more than a survey of some neurophysiological, cognitive, psychosocial and clinical experimental data, the consideration of which presumably leads one to the conclusion that behavior is strictly neuronic. This (...) extensive survey of research data reads like a textbook in Introductory Psychology, for Lohr details experimental studies that are familiar to every college freshman. We hear once again of Kleitman’s sleep experiments, Harlow’s surrogate mothers, even Pavlov’s dogs. Yet, not only is this analysis boring, it is quite defective. Lohr relies solely on these classic experiments in order to argue his thesis; he seems largely to be ignorant of recent experimental research which directly affects his position. This fact is painfully evident both in his discussion of the Central Nervous System and in his treatment of clinical research. Concerning the CNS, Lohr does not take into account Moruzzi and Jouvet’s studies of the ARAS, the recent interest in the hippocampus and the work of Spencer, Thompson and Nielson on the neuronic basis of learning. Lohr’s clinical data are taken, almost exclusively, from the 1950 edition of Coleman’s textbook—an undergraduate primer in abnormal behavior. Yet, even if Lohr were conversant with recent physiological and clinical research it would be impossible to verify his conclusions independently since he provides not one footnote in 513 pages of technical discussion. There are occasional references to specific experiments but by author only; he does not offer dates or source of publication for any of the studies he cites. Moreover, Lohr provides no index and only a nominal bibliography whose omissions are more notable than its entries. These infractions of scholarly courtesy are, however, merely remote indications of the deeper difficulty. From his inadequate survey of experimental research Lohr concludes that an understanding of behavior as exclusively neuronic leads us back to "traditional values" once discarded by psychologists who thought their research explained away "innate tendencies." Lohr argues that "the institutions [i.e., social values] which have evolved do not reflect an artificial set of conditions imposed upon man." Rather, the shape of our nervous system forces upon us certain limits and therefore certain objective moral values. Physiological processes thus "determine" higher order behavior in that they provide an objective matrix from which certain kinds of behavior can be judged aberrant. Hence belief in God, and freedom of the will, insofar as these elements are entailed by objective moral standards, are respectable, even desirable, accoutrements of Lohr’s "mechanistic metaphysics." This reconstruction of morals on the basis of biology suggests a close parallel with certain 19th century evolutionist-philosophers, Spencer, Haeckel and Fiske being, perhaps, the most prominent of the school. These Victorian biologist-philosophers were much more certain of a direct link between neural processes and high-order behavior than their late 20th century counterparts, and they were much more liable to conflate possible social and cultural consequences of their work. Today, however, the type of connection between neural activity and higher order behavior is much less obvious due to more sophisticated research techniques and a more critical lay public. Lohr, as we have noted, does as little justice to these new techniques and trends as Spencer would have done. He completely ignores significant research and virtually all philosophical discussion concerning mind-brain identity. As a consequence, The Mechanics of the Mind fits the same genre as Spencer’s Synthetic Philosophy and Haeckel’s Riddle of the Universe—neither good science nor good philosophy.—J. F. (shrink)